Relationships Between Expression Of TMEM16A In Pasmcs And Vasoconstriction Of Pulmonary Arteries In Rats With Pulmonary Hypertension Induced By High Blood Flow

Objective The aim is to investigate the expression of TMEM16A in PASMCs and its role in the pulmonary arterial constriction of high pulmonary blood flow rats.Methods 24 SD rats were divided randomly into 3 groups:shunt group、 sham group and normal group. Aortocaval shunting rat models were built in shunt group. The same operation were carried on the rats of sham group except the shunting step. The rats of normal group were dealt with nothing special. All the rats were raised in the same condition for 11 weeks. The pathological sections of lung tissues were made to identify whether the rat models were successfully built The pulmonary arteries were separated. RT-PCR, Western Blotting, and isometric tension measurements of pulmonary arteries were performed to determine whether there exist relationships between the expression of TMEM16A and the vasoconstriction of PAs in rats with pulmonary hypertension induced by high blood flow.Results 1.The rat models of pulmonary hypertension induced by high pulmonary blood flow:Typical pathological changes of lung tissues of rats in model group can be observed through microscope, while the lung tissues of rats in normal group and sham group have no obvious pathological changes.2.The expression of TMEM16A mRNA in PASMCs:The expression level of TMEM16A mRNA in PASMCs of shunt group (2.77±0.24) are higher than that of normal group (1.00±0.00) and sham group (0.91±0.04), t=16.09, t=16.91, P< 0.05, but there are no evident differences between shunt group and sham group, t=0.82, P>0.05.3. The expression of TMEM16A protein in PASMCs: The expression level of TMEM16A protein in PASMCs of shunt group (0.70±0.19)are higher than that of normal group (0.20±0.12)and sham group (0.25±0.08), t=7.14, t=6.43, P< 0.05, but there are no evident differences between shunt group and sham group, t=0.71, P>0.05.4.The contractility of PAs evoked by the agonist:The contractility of PAs of shunt group (5.75±1.39) are higher than that of normal group (2.81±0.53) and sham group (2.84±0.49), t=6.44,t=6.44, P< 0.05, but there are no evident differences between shunt group and sham group, t=0.06, P> 0.05.5.The relaxation rates after the applying of T16Ainh-A01 on the contractile PAs evoked by the agonist:The relaxation rates of PAs of shunt group [(66.85±5.97)%] are higher than that of normal group [(46.05±10.82)%] and sham group [(46.40±6.66)%], t=5.25, t=5.00, P< 0.05, but there are no evident differences between shunt group and sham group, t=0.10, P>0.05.Conclusion Upregulation of TMEM16A in PASMCs may contribute to the enhanced vasoconstriction of PAs of rats with pulmonary hypertension induced by high blood flow.